Cobalamin (vitamin B12, Cb1) deficiency can be readily induced in fruit bats (Rousettus aegyptiacus) which are deprived of a dietary source of the vitamin in captivity. They develop an illness with neurological complications, resembling those seen in human pernicious anemia, but without hematological complications. The features of this potential animal model for study of human Cb1 deficiency will be further investigated along the following lines in cb1-deficient and replete bats. Nutritional studies will be extended to compare the effects of cb1, methionine and choline in preventing the neurological changes. Biochemical studies will be carried out to assess whether methylmalonyl CoA mutase or methionine synthetase is the key enzyme in relation to the role of cb1 in the nervous system. The origin and fate of organic acids found in urine in cb1 deficiency will be investigated, and the incorporation of radiolabelled propionate and methylmalonate into myelin lipids will be measured in brain, spinal cord and peripheral nerves. The profile of intracellular forms of cb1 will be analyzed using high performance liquid chromatographpy (hplc). Analysis of nervous system folates will be carried out by hplc and the effects of folate on the neuropathy will be tested. The effects of nitrous oxide, a putative cb1 antagonist, will be compared with the pure nutritional cb1 deficient model. Nerve conduction studies and sensory evoked potentials will be measured in normal and cb1 deficient animals. Structural studies and myelin lipid analysis will be carried out on the brains and spinal cords or bats, including young bats born in captivity. This project seeks to elucidate the metabolic role of cb1 in nervous system tissue and its interaction with other nutrients, notably methionine and folate.